# PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 1993 · $281,491

## Abstract

Members of the genus Rickettsia, including Rickettsia prowazekii,
the etiological agent of epidemic typhus, are unique, even
amongst the obligate intracellular bacterial parasites.  These
organisms grow directly in the cytoplasm, rather than within a
vacuole in the cytoplasm of their eucaryotic host cells.  We
remain committed to understanding the biochemical and
physiological mechanism by which R. prowazekii copes with the
problems and exploits the opportunities of this unique
environmental niche.  This proposal has overall four areas of
research focus.

1.  Phospholipase and penetration:  The putative components of
rickettsial penetration (entry and exit) will be investigated: a)
The substrate specificity and enzyme source (rickettsial or host)
of the phospholipase will be characterized using liposomes which
contain either rickettsial antibodies as a quasi-receptor or
phospholipids labeled in specified acyl groups (as targets for
the rickettsiae or suitable for fusion with host cells).  b) The
elucidation of induced phagocytosis as monitored by actin
polymerization will be correlated with the other facets of
induced phagocytosis.  c) Intracellular damage to organelles by
rickettsiae-dependent phospholipase will be investigated.  d) The
role of phospholipase in the exit of the rickettsiae will be
defined though the use of specific phospholipase inhibitors and
chloramphenicol.  Appropriate phospholipase inhibitors may allow
the rickettsiae to grow and divide in the originally infected
cells but not allow their spread to adjacent cells.  e)
Extracorporeal rickettsial antigens will be characterized and
their role in rickettsial infection in general and with the
phospholipase specifically will be established.  2.  Host Cell
Mutants: We will select, isolate and characterize mutant CHO
cells that do not support the normal entry or growth of R.
prowazekii and therefore survive as uninfected cells in long term
culture in the presence of rickettsiae.  3. Cell Wall: a) The
metabolism of UDPG to insoluble polysaccharide in isolated
rickettsiae and in a cell-free system will be characterized.  b)
The formation of diaminopimelic acid, the role of lysine in this
formation, and the incorporation of these compounds into the
rickettsial murein will be examined in rickettsiae whilst they
are growing in their host cells, i.e., in situ.  4.  Nucleotide
Transport and Metabolism: a) The ATP/ADP Translocase molecule,
from both rickettsiae and E. coli clones expressing the
rickettsial translocase gene, will be purified and characterized
employing reconstitution into proteoliposomes. b) The RNA
Polymerase of R. prowazekii will be characterized with respect to
its subunit composition, its interaction with promoters on the
ricketettsial DNA, and its association with the rickettsial
membrane or ribosomes. c) The Ribonucleotide Reductase of R.
prowazekii will be characterized both in vitro and in situ with
respect to its regulatory properties and as an alternative to the
tr...

## Key facts

- **NIH application ID:** 3125995
- **Project number:** 5R01AI015035-16
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **SAM.gov UEI:** QB12VPNQQFE8
- **Principal Investigator:** HERBERT H WINKLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $281,491
- **Award type:** 5
- **Project period:** 1979-01-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125995

## Citation

> US National Institutes of Health, RePORTER application 3125995, PERMEABILITY OF THE EPIDEMIC TYPHUS RICKETTSIA (5R01AI015035-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125995. Licensed CC0.

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